title: Hemophagocytic lymphohistiocytosis with MUNC13-4 gene mutation or reduced natural killer cell function prior to onset of childhood leukemia.
abstract: Hemophagocytic lymphohistiocytosis (HLH) is a rare histiocytic reactive process due to mutations in the perforin, MUNC13-4 or syntaxin 11 genes, or secondary to malignancy, infection or autoimmune disorder. HLH as a preceding diagnosis to leukemia is rare. We report two cases with progression to acute leukemia, one heterozygous for MUNC13-4 and the other with reduced natural killer (NK) cell function and perforin expression. These defects may predispose to a secondary HLH-like presentation of pre-clinical leukemia or confer increased susceptibility to malignancy. HLH patients with genetic mutations or NK cell function abnormalities need monitoring for future malignancy even if the HLH resolves.
authors.affiliation: Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: Tamara Y
authors.initials: TY
authors.lastname: Chang
authors.forename: Julie
authors.initials: J
authors.lastname: Jaffray
authors.forename: Bruce
authors.initials: B
authors.lastname: Woda
authors.forename: Peter E
authors.initials: PE
authors.lastname: Newburger
authors.forename: G Naheed
authors.initials: GN
authors.lastname: Usmani
mesh_terms: D002675:Child, Preschool; D005260:Female; D006579:Heterozygote; D006801:Humans; D007694:Killer Cells, Natural / Q000473:pathology*; D007948:Leukemia, Monocytic, Acute / Q000209:etiology* / Q000473:pathology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D054353:Perforin / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology* / Q000473:pathology; D011379:Prognosis; D050765:Qa-SNARE Proteins / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D050765:Qa-SNARE Proteins; C507969:UNC13D protein, human; D054353:Perforin